The rodent trigeminal sytem has served as a valuable model of somatosensory development and plasticity for over two decades. Most of these investigations, however, have focussed entirely on the ascending trigeminal pathways, with little attention paid to the maturation of the des cending inputs to th e trigeminal neuraxis or the developmental interactions between the ascending and descending projections. This issue is not t rivial, since it is well known that cortical inputs to thalamic and brainstem nuclei are important in the normal processing in subcortical nuclei, these descending projections may influence (or be influenced by) the development of the ascending trigeminal pathways. We have formulated a series of experiemtns that are designed to address three major hypotheses regarding the normal development, specificity and plasticity of the cortical projections to the thalamus and brainstem. Our first hypothesis is that the rat corticotrigeminal (CT) pathway develops in an ipsilaterial- to-contralateral, rostral-to-caudal sequence in the late prenatal and early postnatal period. We will test this hypothesis with our Specific Aim !, which will use anterograde transport of DiI to establish the status of the developing CT pathway in prenatal and early postnatal rats. Our second hypothesis is that many of the cortical neurons projecting to the brainstem in the early postnatal period terminate in both the ipsilateral and contralateral trigeminal brainstem nucelar complex (TBNC). We further propose that most of the ispsilateral TBNC collaterals of these cortical hneurons are eliminated as a result of competitive interactions with trigeminal primary afferents. We wil test these postualtes with our Specific Aims 2,3 and 4 which will 1) determine the percentage of CT neurons in normal perinatal and adult animals that projecct to both the ipsilateral and contralateral TBNC, 2) assess the role of primary afferent activity in the development and maintenance of the cortical projections to the brainstem and thalamus and 3) examine the role of cortical neuron activity in the development of the corticofugal pathways. The number of cortical neurons projecting to the ipsilateral and contralateral brainstem will be determined by injecting DiI (or fast blue) into either the right or left TBNC and DiO (or fluorogold) into the contralateral brainstem. We will examine the role of primary afferent activity in the development and maintenance of the corticofugal pathways by chronically trimming the vibrissae of the mystacial pad and then labeling the CT and corticothalamic (CTh) projections with WGA-HRP and biocytin. In a related series of experimetns we will determine the role of cortical neuron activity in this process by exposing the cortex to tetrodotoxin in the early postnatal period. Our third hypothesis is that some of the cortical neurons destined to project to teh TBNC send transient collaterals tot he thalamus. We will test this hypothesis with our Specific Aim 5, which will use injections of DiI into the TBNC with simultaneous injections of DiO into the thalamus to identify CT neurons that send collaterals into the thalamus during the formation of the CT tract.